CN106083988A - The pharmaceutical composition of a kind of succimer and medical usage thereof - Google Patents
The pharmaceutical composition of a kind of succimer and medical usage thereof Download PDFInfo
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- CN106083988A CN106083988A CN201610473707.3A CN201610473707A CN106083988A CN 106083988 A CN106083988 A CN 106083988A CN 201610473707 A CN201610473707 A CN 201610473707A CN 106083988 A CN106083988 A CN 106083988A
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J73/00—Steroids in which the cyclopenta[a]hydrophenanthrene skeleton has been modified by substitution of one or two carbon atoms by hetero atoms
- C07J73/001—Steroids in which the cyclopenta[a]hydrophenanthrene skeleton has been modified by substitution of one or two carbon atoms by hetero atoms by one hetero atom
- C07J73/003—Steroids in which the cyclopenta[a]hydrophenanthrene skeleton has been modified by substitution of one or two carbon atoms by hetero atoms by one hetero atom by oxygen as hetero atom
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/194—Carboxylic acids, e.g. valproic acid having two or more carboxyl groups, e.g. succinic, maleic or phthalic acid
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/58—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin
- A61K31/585—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin containing lactone rings, e.g. oxandrolone, bufalin
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- Animal Behavior & Ethology (AREA)
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- Pharmacology & Pharmacy (AREA)
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Abstract
The invention discloses pharmaceutical composition and the medical usage thereof of a kind of succimer, containing succimer and the natural product compound (I) of a kind of novel structure in the pharmaceutical composition of the succimer that the present invention provides, when succimer, compound (I) independent role, immunologic thrombocytopenic purpura had therapeutical effect;When succimer and compound (I) synergy, the therapeutic effect of immunologic thrombocytopenic purpura is significantly improved, the medicine for the treatment of immunologic thrombocytopenic purpura can be developed into, compared with prior art there is prominent substantive distinguishing features and significantly progress.
Description
Technical field
The invention belongs to biomedicine field, relate to the new application of succimer, be specifically related to the medicine of succimer
Compositions and medical usage thereof.
Background technology
Succimer is a kind of antidote, is usually used in clinically treating lead, hydrargyrum, arsenic, stibialism, has decorporation to make copper
With, it is adaptable to the treatment of hepatolenticular degeneration.
Up to now, there is not yet succimer and pharmaceutical composition thereof relevant to immunologic thrombocytopenic purpura
Property report.
Summary of the invention
It is an object of the invention to provide the pharmaceutical composition of a kind of succimer, containing two mercaptos in this pharmaceutical composition
Succinic acid and the natural product of a kind of novel structure, succimer and this natural product can Synergistic treatment immunity platelet subtract
Few property purpura.
The above-mentioned purpose of the present invention is achieved by techniques below scheme:
A kind of compound (I) with following structural formula,
The pharmaceutical composition of a kind of succimer, including succimer, compound as claimed in claim 1 (I)
Pharmaceutically acceptable carrier, is prepared as the dosage form needed.
Further, pharmaceutically acceptable carrier include diluent, excipient, filler, binding agent, wetting agent,
Disintegrating agent, absorption enhancer, surfactant, absorption carrier or lubricant.
Further, described dosage form include tablet, capsule, oral liquid, suck agent, granule, electuary, pill, powder,
Unguentum, sublimed preparation, suspensoid, powder, solution, injection, suppository, spray, drop or patch.
The preparation method of above-claimed cpd (I), comprises following operating procedure: Herba Hyperici Monogyni is pulverized by (a), with 75~
85% alcohol heat reflux extract, united extraction liquid, be concentrated into without alcohol taste, successively use petroleum ether, ethyl acetate and water saturated just
Butanol, before immunoassay, respectively obtains petroleum ether extract, acetic acid ethyl ester extract and n-butyl alcohol extract;N-butyl alcohol in (b) step (a)
Take thing macroporous resin remove impurity, first with 8 column volumes of 25% ethanol elution, then with 12 column volumes of 70% ethanol elution, collect
70% eluent, concentrating under reduced pressure obtains 70% ethanol elution concentrate;70% ethanol elution concentrate positive in (c) step (b)
Silica gel separates, and obtains 4 groups with the methylene chloride-methanol gradient elution that volume ratio is 85:1,45:1,25:1 and 15:1 successively
Point;D in () step (c), component 4 separates further by purification on normal-phase silica gel, be the dichloromethane of 20:1,15:1 and 1:1 by volume ratio successively
Alkane-methanol elution gradient obtains 3 components;E reverse phase silica gel that in () step (d), component 2 is bonded by octadecylsilane separates,
With the methanol aqueous solution isocratic elution that concentration expressed in percentage by volume is 72%, collecting 10~16 column volume eluents, eluent reduces pressure
It is concentrated to give compound (I).
Further, in the preparation method of compound (I), described macroporous resin is D101 type macroporous adsorbent resin.
The above-claimed cpd (I) application in the medicine of preparation treatment immunologic thrombocytopenic purpura.
The pharmaceutical composition of above-mentioned succimer is in the medicine of preparation treatment immunologic thrombocytopenic purpura
Application.
Advantages of the present invention:
Containing succimer and the sky of a kind of novel structure in the pharmaceutical composition of the succimer that the present invention provides
So product, when succimer, compound (I) independent role, has therapeutical effect to immunologic thrombocytopenic purpura;Two
When mercapto succinic acid and compound (I) synergy, the therapeutic effect of immunologic thrombocytopenic purpura is significantly improved, permissible
Develop into the medicine for the treatment of immunologic thrombocytopenic purpura.
Detailed description of the invention
Further illustrate the essentiality content of the present invention below in conjunction with embodiment, but do not limit the present invention with this and protect model
Enclose.Although the present invention being explained in detail with reference to preferred embodiment, it will be understood by those within the art that, can be right
Technical scheme is modified or equivalent, without deviating from the spirit and scope of technical solution of the present invention.
Embodiment 1: compound (I) separates preparation and structural identification
Separation method: Herba Hyperici Monogyni (2kg) is pulverized by (a), extracts (15L × 3 time) with 80% alcohol heat reflux, merges
Extracting solution, is concentrated into without alcohol taste (3L), successively by petroleum ether (3L × 3 time), ethyl acetate (3L × 3 time) and water saturated positive fourth
Alcohol (3L × 3 time) extracts, and respectively obtains petroleum ether extract, acetic acid ethyl ester extract and n-butyl alcohol extract;(b) step (a)
Middle acetic acid ethyl ester extract D101 type macroporous resin remove impurity, first with 8 column volumes of 25% ethanol elution, then washes with 70% ethanol
De-12 column volumes, collect 70% eluent, and concentrating under reduced pressure obtains 70% ethanol elution concentrate;70% ethanol in (c) step (b)
Eluting concentrate with purification on normal-phase silica gel separate, successively with volume ratio be 85:1 (10 column volumes), 45:1 (8 column volumes), 25:1
The methylene chloride-methanol gradient elution of (10 column volumes) and 15:1 (8 column volumes) obtains 4 components;In (d) step (c)
Component 4 separates further by purification on normal-phase silica gel, successively with volume ratio be 20:1 (10 column volumes), 15:1 (8 column volumes) and 1:1
The methylene chloride-methanol gradient elution of (6 column volumes) obtains 3 components;E in () step (d), component 2 uses octadecylsilane
The reverse phase silica gel of bonding separates, and with the methanol aqueous solution isocratic elution that concentration expressed in percentage by volume is 72%, collects 10~16 cylinders
Long-pending eluent, eluent is concentrated under reduced pressure to give compound (I) (HPLC normalization purity is more than 98%).
Structural identification: HR-ESI-MS shows [M+H]+For m/z 523.3022, can obtain molecular formula in conjunction with nuclear-magnetism feature is
C32H42O6, degree of unsaturation is 12.Hydrogen nuclear magnetic resonance modal data δH(ppm, DMSO-d6, 600MHz): H-1 (6.06, d, J=
12.9Hz), H-2 (5.88, d, J=12.9Hz), H-4 (4.35, qd, J=6.5,4.4Hz), H-5 (2.34, dd, J=4.4,
3.8Hz), H-6 (2.59, dd, J=4.2,3.8Hz), H-7 (2.48, dd, J=4.2,3.7Hz), H-8 (1.85, d, J=
3.7Hz), and H-11 (1.50, m), H-11 (2.10, m), H-12 (1.63, m), H-12 (1.71, m), H-15 (1.28, m), H-15
(2.34, dd, J=14.9,7.3Hz), H-16 (5.32, m), H-16b (2.05, s), H-17 (2.51, m), H-18 (1.08, s),
H-19 (0.97, d, J=4.3Hz), and H-19 (1.98, d, J=4.3Hz), H-21 (1.81, s), H-22 (6.61, s), H-24a
(5.85, s), H-24a (6.04, s), H-25 (2.88, m), H-26 (1.03, d, J=6.6Hz), H-27 (1.11, d, J=
6.6Hz), and H-28 (1.27, d, J=6.7Hz), H-30 (0.99, s);Carbon-13 nmr spectra data δC(ppm, DMSO-d6,
150MHz): 150.2 (CH, 1-C), 119.6 (CH, 2-C), 168.5 (C, 3-C), 73.5 (CH, 4-C), 52.8 (CH, 5-C),
56.7 (CH, 6-C), 55.6 (CH, 7-C), 49.2 (CH, 8-C), 30.2 (C, 9-C), 37.0 (C, 10-C), 28.5 (CH2, 11-
C), 32.6 (CH2, 12-C), 45.2 (C, 13-C), 47.3 (C, 14-C), 46.9 (CH2, 15-C), 77.1 (CH, 16-C), 170.2
(C, 16a-C), 22.3 (CH3, 16b-C), 59.5 (CH, 17-C), 18.5 (CH3, 18-C), 32.5 (CH2, 19-C), 162.4 (C,
20-C), 16.8 (CH3, 21-C), 126.6 (CH, 22-C), 194.8 (C, 23-C), 154.3 (C, 24-C), 119.8 (CH2, 24a-
C), 29.5 (CH, 25-C), 22.1 (CH3, 26-C), 21.8 (CH3, 27-C), 18.8 (CH3, 28-C), 20.1 (CH3, 30-C).
1715cm in IR spectrogram-1With 1694cm-1Absorption band shows to there is carbonyl and conjugation carbonyl in this compound structure;UV spectrogram
In absorption maximum 207nm and 245nm explanation structure in there is conjugated double bond.Hydrogen spectrum nuclear magnetic data shows in this structure unsaturated
Degree is by three C-C double bond structures, three carbonyl structures and six cyclic skeleton compositions.Carbon spectrum nuclear magnetic data composes number with DEPT
According to showing in this compound structure containing 32 carbon, wherein there are seven methyl, five methylene (an olefinic methylene), 11
Individual methine (three olefinic methines, four oxygen-containing methines), nine quaternary carbons (ketone group, two ester carbonyl groups, two olefinics
Quaternary carbon).Two High-Field proton signal (δH0.97 and δH1.98) coupling constant is 4.3Hz, is the card that there is cyclopropane moiety
According to;Proton signal δH2.59 (1H, d, J=4.2,3.8Hz, H-6), 2.48 (1H, dd, J=4.2,3.7Hz, H-7) and corresponding
Carbon signal δC56.7 (C-6) and 55.6 (C-7) show that this compound contains glycidyl structure.Additionally, can by nuclear magnetic data
Know that this compound is possibly together with the α, seven yuan of lactonic ring [δ of β-unsaturation with a methyl chainsH6.06 (d, J=12.9Hz, H-
1), 5.88 (d, J=12.9Hz, H-2), 4.35 (qd, J=6.5,4.4Hz, H-4), 2.34 (dd, J=4.4,3.8Hz, H-5),
1.27 (3H, d, J=6.7Hz, H-28);δC150.2 (C-1), 119.6 (C-2), 168.5 (C-3), 73.5 (C-4), 52.8 (C-
5), 37.0 (C-10), 18.8 (C-28)] and acetoxyl group [δH2.05 (s, H-16b, 3H);δC170.2 (C-16a), 22.3 (C-
16b)].In HMBC spectrum, H-16 (5.32) and C-16a (δC170.2) dependency shows acetoxyl group and C-16 (δC77.1) position
It is connected.H-4 (δ is resolved by NOESY modal dataH 4.25)、H3-28(δH1.27) with H-5 (δH2.34) and H-6 (δH2.59)
Relation can illustrate 28-methyl Relative configuration.Comprehensive hydrogen spectrum, carbon spectrum, HMBC spectrum and NOESY spectrum, and document is about phase
Closing types of nuclear magnetic data, can substantially determine that this compound is as follows, spatial configuration is determined by ECD test further, theoretical
It is worth basically identical with experiment value.
This compound chemical formula and carbon atoms numbered are as follows:
Embodiment 2: pharmacological action
The present embodiment uses by obtaining BALB/C mice platelet antibody, is inoculated into Cavia porcellus, obtains Cavia porcellus and resists little
Mus platelet antibody (APS), sets up immunologic thrombocytopenic purpura animal model by APS lumbar injection BALB/C mice,
Observe the anti-immune blood of the aspects such as medicine makes platelet count rise, Spleen coefficient reduces, bone marrow maturation megalokaryocyte increases
Platelet minimizing property purpura effect.
1, materials and methods
1.1 animal
BALB/C mice, body weight 18~23g, male and female half and half, SPF level, purchased from medical animal experiment center, Guangdong Province;Globefish
Mus, female, body weight 350g, regular grade, purchased from medical animal experiment center, Guangdong Province.
1.2 reagent and sample
Succimer is purchased from Nat'l Pharmaceutical & Biological Products Control Institute.Compound (I) is made by oneself, and preparation method is shown in embodiment 1.
Incomplete Freund's adjuvant (Beijing ancient cooking vessel Bioisystech Co., Ltd, DH-1341-1), (Tianjin BASF chemical industry has EDTA-Na2
Limit company, analytical pure), Ethylurethanm (Guangdong Guanghua Science and Technology Co., Ltd., analytical pure), oxalic acid ammonia (Guangdong brilliance high-tech stock
Part company limited, analytical pure), prednisone (northwest the second synthesis pharmaceutical factory, medicinal specification), Switzerland's staining reagent (Beijing Bo Run
Lai Te Science and Technology Ltd.).
1.3 instrument
Automatic blood analyzer (method, ABXPENTRA60), (Sai Duolisi scientific instrument (Beijing) have electronic balance
Limit company, BSA1245), thermostat water bath (Changzhou Ao Hua Instrument Ltd., HA-4), centrifugal precipitation mechanism (Asia, Shanghai Rong Shenghua
Instrument plant, 80-2), Constant Temp. Oven (Guangzhou Kang Heng Instrument Ltd., 101-A), (Nikon instrument is limited for microscope
Company, Nikoneclipsee100).
The 1.4 sero-fast preparations of Cavia porcellus antiplatelet
Taking the BALB/C mice of health to pluck eyeball and take blood, stand half an hour, 8000rpm/min is centrifuged 10min, takes upper strata
Serum 1500rpm/min is centrifuged 15min, takes upper serum 900rpm/min and is centrifuged 10min, takes upper serum 3000rpm/min
Centrifugal 10min, discards serum, obtains bottom precipitation platelet, adds 1% oxalic acid ammonia 1mL, stands 5min, 3000rpm/min centrifugal
10min, discards supernatant liquid, bottom platelet brine three times, with normal saline dilution to concentration be 1~2 ×
109/ L, is mixed into Freund's complete adjuvant platelet antigen with Freund's complete adjuvant and incomplete Freund's adjuvant by 1:1 respectively and mixes
Thing and not Freund's complete adjuvant platelet antigen mixture, standby;Take healthy guinea pig 10, help completely in the 1st week injection Freund
Agent platelet antigen mixture is in its extremity, abdomen stock, back, subcutaneous, and often place's injection 100 μ L, in the same agent of injection in the 2nd, 3,4 weeks
The not Freund's complete adjuvant platelet antigen mixture of amount.4th weekend with 20% urethane 2mL abdominal cavity depending on penetrating anaesthetized guinea pig, the heart
The dirty blood that takes, 1500rpm/min is centrifuged 10min, takes upper serum, and remaining whole blood continues 3000rpm/min and is centrifuged 10min, merges
Twice gained serum, obtains Cavia porcellus anti-mouse platelet serum APS, and-20 DEG C of preservations are standby.Self-control diameter 9cm agarose plate,
Quincunx hole, interstitial hole dropping platelet suspension (500 × 10 is broken into card punch9/ L), holes around add 1:2,1:4,1:8,1:
16, the Cavia porcellus anti-mouse platelet serum of 1:32,1:64 difference titer.37 DEG C of incubation 24h, observe precipitation arc, and detection is anti-
Serum titer.
Prepared by 1.5 mice group and model
Mice is randomly divided into 6 groups, often group 12, and respectively Normal group, model control group, positive controls is (strong
Song Long group, 2.25mg kg-1) and succimer group (120mg kg-1), compound (I) group (120mg kg-1), two mercapto fourths
Diacid and compound (I) compositions group [60mg kg-1Succimer+60mg kg-1Compound (I)].Take out-20 DEG C of guarantors
The APS deposited, 56 DEG C of water-bath 30min inactivate complement, and by the titer of normal saline dilution to 1:4, mice carries out lumbar injection.In 0,
2,4,6,8,10d inject the antiserum of dilution according to 100 μ g/20g mouse peritoneals, every 2d duplicate injection once, to maintain blood little
The lasting reduction of plate.After the 1st injection APS, administration group presses above-mentioned corresponding dosage intraperitoneal injection, Normal group and mould
Type matched group injecting normal saline.
1.6 platelet count experiments
2h after being administered for 10th day, plucks eyeball and takes blood, detect platelet count.
1.7 Spleen coefficient determination experiments
Dissect and take out liver, weigh, calculate Spleen coefficient.
1.8 Megakaryocytic classification number determination experiments
Peel off femur, take out bone marrow smear, Switzerland's staining dyeing, calculate Megakaryocytic classification number
1.9 statistical method
Experimental data mean ± standard deviation (x ± s) represents, application SPSS18.0 version statistical software carries out single factor test variance
Analyze and t checks, statistically significant for difference with P < 0.05.
2, experimental result
2.1 impacts on immunologic thrombocytopenic purpura model mice platelet count
Comparing with Normal group, model control group mouse platelets counting substantially reduces (P < 0.01);With model comparison
Group compares, and succimer significantly raises (P < 0.01) with compound (I) compositions group and positive controls platelet count;
Comparing with model control group, succimer group, compound (I) group mouse platelets counting raises (P < 0.05).The results are shown in Table
1。
2.2 impacts on immunologic thrombocytopenic purpura model mice Spleen coefficient
With Normal group ratio, the Spleen coefficient of model control group mice is significantly raised (P < 0.01).With model control group
Relatively, succimer significantly reduces (P < 0.01) with compound (I) compositions group and positive controls mouse spleen coefficient;
Comparing with model control group, succimer group, compound (I) group mouse spleen coefficient significantly reduces (P < 0.05).
Result of the test is shown in Table 1.
2.3 impacts on immunologic thrombocytopenic purpura model mice macrophage
Comparing with Normal group, the full-brown macrophage number of model control group mice is decreased obviously (P < 0.01).With mould
Type matched group compares, succimer and compound (I) compositions group and the full-brown macrophage digital display of positive controls mice
Write and raise (P < 0.01);Compare with model control group, the full-brown macrophage number of succimer group, compound (I) group mice
Raise (P < 0.05).
Result of the test is shown in Table 1.
Table 1 is on immunologic thrombocytopenic purpura model mice platelet, Spleen coefficient and the impact of macrophage
Purpura is one of the most common bleeding, is owing to there is antiplatelet antibody in the patient.At present
The inside and outside main first-line drug for the treatment of for purpura is hormone medicine such as prednisone, cortisone, prednisolone etc., or vein
Injection human normal immunoglobulin and splenectomy etc..In terms of pharmacological point, hormone is used to carry out treatment mainly by suppressing blood
The phagocytosis of platelet, the generation of suppression platelet antibody.The immune organs such as spleen are the main place producing platelet antibody, pass through
Produce platelet antibody and destroy phagocytosis platelet, then excite complement system, outside knee joint blood vessel classical, non-classical, destroy blood little
Plate, causes subcutaneous hemorrhage phenomenon.But according to clinical statistics, using hormone medicine treatment to have relapse rate high, side effect is many, and the course for the treatment of is long
Etc. shortcoming, patient needs Long-term taking medicine to treat.According to statistics, only 10~20% do not have rebound phenomenon after patient's drug withdrawal.Use spleen
Excision treatment, logical for intractable purpura is ineffective, is difficult to for a long time for Low patient, particularly elderly patient
Heavy dose accepts the impact treatment of hormone medicine.
The above results shows, when succimer, compound (I) independent role, to immunologic thrombocytopenic purpura
There is therapeutical effect;When succimer and compound (I) synergy, the treatment to immunologic thrombocytopenic purpura is imitated
Fruit significantly improves, and can develop into the medicine for the treatment of immunologic thrombocytopenic purpura.
The effect of above-described embodiment indicates that the essentiality content of the present invention, but does not limit the protection of the present invention with this
Scope.It will be understood by those within the art that, technical scheme can be modified or equivalent,
Essence and protection domain without deviating from technical solution of the present invention.
Claims (8)
1. a compound (I) with following structural formula,
2. the pharmaceutical composition of a succimer, it is characterised in that: include succimer, as claimed in claim 1
Compound (I) and pharmaceutically acceptable carrier, be prepared as the dosage form needed.
The pharmaceutical composition of succimer the most according to claim 2, it is characterised in that: pharmaceutically acceptable carries
Body includes that diluent, excipient, filler, binding agent, wetting agent, disintegrating agent, absorption enhancer, surfactant, absorption carry
Body or lubricant.
The pharmaceutical composition of succimer the most according to claim 2, it is characterised in that: described dosage form include tablet,
Capsule, oral liquid, suck agent, granule, electuary, pill, powder, unguentum, sublimed preparation, suspensoid, powder, solution, injection
Agent, suppository, spray, drop or patch.
5. the preparation method of the compound (I) described in claim 1, it is characterised in that comprise following operating procedure: (a) will pass through
Leaf Radix Hyperici Monogyni (Herba Hyperici Monogyni) pulverize, with 75~85% alcohol heat reflux extract, united extraction liquid, be concentrated into without alcohol taste, successively use petroleum ether, second
Acetoacetic ester and water saturated n-butanol extraction, respectively obtain petroleum ether extract, acetic acid ethyl ester extract and n-butyl alcohol extract;
B in () step (a), n-butyl alcohol takes thing macroporous resin remove impurity, first with 8 column volumes of 25% ethanol elution, then wash with 70% ethanol
De-12 column volumes, collect 70% eluent, and concentrating under reduced pressure obtains 70% ethanol elution concentrate;70% ethanol in (c) step (b)
Eluting concentrate purification on normal-phase silica gel separates, successively with the methylene chloride-methanol ladder that volume ratio is 85:1,45:1,25:1 and 15:1
Degree affords 4 components;D in () step (c), component 4 separates further by purification on normal-phase silica gel, successively with volume ratio be 20:1,
The methylene chloride-methanol gradient elution of 15:1 and 1:1 obtains 3 components;Component 2 octadecylsilane key in (e) step (d)
The reverse phase silica gel closed separates, and with the methanol aqueous solution isocratic elution that concentration expressed in percentage by volume is 72%, collects 10~16 column volumes
Eluent, eluent is concentrated under reduced pressure to give compound (I).
The preparation method of compound the most according to claim 5 (I), it is characterised in that: described macroporous resin is D101 type
Macroporous adsorbent resin.
7. the application in the medicine of preparation treatment immunologic thrombocytopenic purpura of the compound (I) described in claim 1.
8. the pharmaceutical composition of the arbitrary described succimer of claim 2~4 is in preparation treatment immunity thrombocytopenia
Application in the medicine of property purpura.
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CN106279344A (en) * | 2016-08-14 | 2017-01-04 | 吴芊葭 | A kind of native compound separated from Radix Saposhnikoviae and preparation method thereof, medical applications |
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Application publication date: 20161109 |